Oncologic orphan drugs approved in the EU – do clinical trial data correspond with real-world effectiveness?

Schuller, Yvonne; Biegstraaten, Marieke; Hollak, Carla E. M.; Klümpen, Heinz-Josef; Gispen-de Wied, Christine C.; Stoyanova-Beninska, Violeta

doi:10.1186/s13023-018-0900-9

Orphanet Journal of Rare Diseases

Table 4 Characteristics of pivotal studies (COMPASS)

From: Oncologic orphan drugs approved in the EU – do clinical trial data correspond with real-world effectiveness?

Drug	Indication	Pivotal study	Primary endpoint	Study phase	Control	Design	Performance status [16]	No. of patients	OS effect in months	QoL effect
Imatinib	GIST	Demetri 2002 [36] DeMatteo 2009 [21]	ORR RFS	II III	Imatinib (different dose) Placebo	Rand. OL Rand. DB	ECOG ≤3 ECOG ≤2	147 713	n/a n/a	NE NE
Imatinib	DFSP	Heinrich 2008 [39]	ORR	II	None	Single-arm	ECOG ≤2	18	NE	NS
Mitotane	Adrenocortical carcinoma	Several pivotal studies	OS, PFS, ORR	n/a	n/a	n/a	n/a	> 500	n/a	n/a
Sunitinib^a	GIST	Demetri 2006 [22]	TTP	III	Placebo	Rand. DB	ECOG ≤1	312	n/a	NE
Sunitinib	RCC	Motzer 2006 [40] Motzer 2007 [31]	ORR PFS	II III	None IFN-α	Single-arm Rand. OL	ECOG ≤1 ECOG ≤1	106 750	n/a n/a	NE Improved
Sorafenib^a	RCC	Escudier 2007 [24]	OS	III	Placebo	Rand. DB	ECOG ≤1	903	n/a	NS
Sorafenib	HCC	Llovet 2008 29	OS, TTP	III	Placebo	Rand. DB	ECOG ≤2	602	2.8	NE
Sorafenib	Thyroid carcinoma	Brose 2014 [20] (DECISION)	PFS	III	Placebo	Rand. DB	ECOG ≤2	417	n/a	NS
Temsirolimus	RCC	Hudes 2007 [26] (ARCC)	OS	III	IFN-α	Rand. OL	Karnofsky ≥60 (ECOG 1)	626	3.6	NS
Trabectedin	STS	Demetri 2009 [35]	TTP	II	Trabectedin (different dose)	Rand. OL	ECOG ≤1	266	2.1 (NS)	NE
Trabectedin	Ovarian cancer	Monk 2010 [29]	PFS	III	Single-agent PLD	Rand. OL	ECOG ≤2	672	n/a	NS
Mifamurtide	Osteosarcoma	Meyers 2005 [28]	EFS	III	Ifosfamide	Rand. OL (factorial)	Not reported	678	n/a	NE
Everolimus^a	RCC	Motzer 2008 [30]	PFS	III	Placebo	Rand. DB	Karnofsky ≥70 (ECOG 1)	416	n/a	NS
Cabozantinib	Medullary thyroid cancer	Elisei 2013 [23]	PFS	III	Placebo	Rand. DB	ECOG ≤2	330	n/a	NE
Olaparib	Ovarian cancer	Ledermann 2012 [37]	PFS	II	Placebo	Rand. DB	ECOG ≤2	265	n/a	NS
Ramucirumab	Gastric cancer	Wilke 2014 [34] (RAINBOW) Fuchs 2014 [25] (REGARD)	OS OS	III III	Placebo Placebo	Rand. DB Rand. DB	ECOG ≤1 ECOG ≤2	665 355	2.2 1.4	NS NS
Dinutuximab^a	Neuroblastoma	Study not yet published [19]	EFS	III	Isotretinoin	Rand. OL	Karnofsky ≥50 (ECOG 2)	230	n/a	NE
Lenvatinib	Thyroid cancer	Schlumberger 2015 [32]	PFS	III	Placebo	Rand. DB	ECOG ≤3	392	n/a	NE
Olaratumab	STS	Tap 2016 [38]	PFS	Ib/II	Doxorubicin	Rand. OL	ECOG ≤2	133	11.8	NE
Nanoliposomal irinotecan	Pancreatic cancer	Wang-Gillam 2016 [33]	OS	III	Fluorouracil and folinic acid	Rand. OL	Karnofsky ≥70(ECOG 1)	417	1.9	NS

COMPASS Clinical Evidence of Orphan Medicinal Products – an ASSessment tool, DB double-blind, DFSP Dermatofibrosarcoma protuberans, ECOG Eastern Cooperative Oncology Group, EFS event-free survival, GIST gastrointestinal stromal tumor, HCC hepatocellular carcinoma, IFN-α interferon alfa, NE not evaluated, NS no significant improvement, ORR overall response rate, OS overall survival, PFS progression-free survival, PLD pegylated liposomal doxorubicin, pNET pancreatic neuroendocrine tumor, PLD pegylated liposomal doxorubicin, Rand DB randomized double-blind, Rand OL randomized open-label, RCC renal cell carcinoma, STS soft tissue sarcoma, TTP time to tumor progression
^a Pivotal study was terminated early

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ISSN: 1750-1172

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